Tumor-associated antigens (NSCLC) (TAA)

Tumor-associated antigens (TAAs) presented via gp96-Ig-expressing NSCLC-derived cells refer to the diverse array of proteins and peptides specific to non-small cell lung cancer (NSCLC) that are delivered to the immune system using a specialized heat shock protein chaperone platform. In this therapeutic approach, an allogeneic NSCLC cell line is genetically engineered to secrete gp96 (HSP90B1) fused to an immunoglobulin Fc domain (gp96-Ig). This fusion protein functions as a powerful adjuvant and carrier, chaperoning the full repertoire of intracellular TAAs from the vaccine cell and delivering them to professional antigen-presenting cells (APCs) via the CD91 receptor (Strbo et al., 2013). This process facilitates the cross-presentation of these antigens on MHC class I molecules, thereby stimulating a robust, polyvalent CD8+ T-cell response capable of recognizing and killing the patient's own tumor cells. This strategy is the basis for the immunotherapy HS-110 (viagenpumatucel-L), which aims to overcome tumor heterogeneity by targeting multiple antigens simultaneously rather than a single protein (Raez et al., 2015). Clinical studies have explored this target in combination with checkpoint inhibitors to enhance the immune system's ability to infiltrate and destroy lung tumors (ClinicalTrials.gov, NCT02143466). The use of gp96-Ig ensures that the antigens are delivered in a highly immunogenic context, bypassing the need for identifying specific patient neoantigens.

Other names

NSCLC-associated antigensTumor antigensgp96-chaperoned peptidesCancer-testis antigensNeoantigens

The gp96-Ig fusion protein acts as a molecular chaperone that binds a broad spectrum of tumor-associated antigens (TAAs) within the endoplasmic reticulum of the vaccine cell. Upon secretion, the gp96-Ig-TAA complex is recognized by CD91 (low-density lipoprotein receptor-related protein 1) on professional antigen-presenting cells (APCs), such as dendritic cells. This interaction triggers receptor-mediated endocytosis, leading to the cross-presentation of the chaperoned TAAs on MHC class I molecules, which subsequently activates a polyvalent CD8+ cytotoxic T-lymphocyte (CTL) response against the patient's tumor cells (Strbo et al., 2013; Raez et al., 2015).